Arylsulphonamides, pharmaceutical compositions containing these compounds and processes for preparing them

Abstract

The invention relates to new arylsulphonamides of the formula <IMAGE> (I) (wherein A, B and R1 to R6 are as defined in claim 1, the enantiomers, the cis- and trans-isomers thereof where R4 and R5 together represent a carbon-carbon bond, and the addition salts thereof, more particularly for pharmaceutical use the physiologically acceptable addition salts thereof with inorganic or organic bases, if R6 represents a hydroxy group) which have useful pharmacological properties, particularly antithrombotic activities and thromboxane-mediating activities. Furthermore, the new compounds are also thromboxane antagonists (TRA) and thromboxane synthesis inhibitors (TSH). They also have an effect on PGE2 production.

What is claimed is: 
     
       1. Arylsulphonamides of formula ##STR11## wherein R 1  represents a phenylalkyl, trialkylphenyl, tetramethylphenyl or pentamethylphenyl group, a thienyl group optionally substituted by a halogen atom or an alkyl group, or a phenyl group which may be mono-substituted by a nitro group or mono- or disubstituted by a halogen atom or by an alkyl, trifluoromethyl or alkoxy group, the substituents being identical or different, R 2 , R 4  and R 5 , which may be identical or different, each represents a hydrogen atom or an alkyl group or   R 2  represents a hydrogen atom or an alkyl group and R 4  and R 5  together represent a carbon-carbon bond,   R 3  represents a pyridyl group optionally substituted by an alkyl group,   R 6  represents a hydroxy, alkoxy, amino, alkylamino or dialkylamino group,   A represents a group of formula ##STR12## wherein R 7  represents a hydrogen atom or an alkyl group,   X represents an alkyl-substituted imino group or an oxygen or sulphur atom, the --CHR 7  -- group being attached to the --NR 2  -- group, and   B represents a carbon-carbon bond or a straight-chained C 1-4  alkylene group optionally substituted by one or two alkyl groups, whilst all the alkyl and alkoxy moieties mentioned hereinbefore may each contain 1 to 3 carbon atoms, the enantiomers thereof, the cis- and trans-isomers thereof where R 4  and R 5  together represent a carbon-carbon bond, or the addition salts thereof.     
     
     
       2. Arylsulphonamides of formula I according to claim 1 wherein R 1  represents a benzyl, thienyl, chlorothienyl, dichlorophenyl, dimethoxyphenyl, tetramethylphenyl or pentamethylphenyl group or a phenyl group optionally substituted by a fluorine or chlorine atom or by a nitro, methyl or trifluoromethyl group,   R 2 , R 4  and R 5  each represent a hydrogen atom or a methyl group or   R 2  represents a hydrogen atom or a methyl group and R 4  and R 5  together represent a carbon-carbon bond,   R 3  represents a pyridyl group,   R 6  represents a hydroxy or methoxy group,   A represents a group of formula ##STR13## wherein R 7  represents a hydrogen atom and   X represents a sulphur atom or an N-methylimino group, the --CHR 7  -- group being linked to the --NR 2  -- group, and   B represents a carbon-carbon bond or a straight-chained C 2-4  alkylene group, the enantiomers, the cis and trans isomers where R 4  and R 5  together form a carbon-carbon bond, or the addition salts thereof.     
     
     
       3. Physiologically acceptable addition salts of the compounds according to claims 1 or 2 with inorganic or organic bases. 
     
     
       4. Pharmaceutical composition containing as active substance a compound according to claim 1 or a physiologically acceptable addition salt thereof optionally together with one or more inert carriers and/or diluents. 
     
     
       5. Pharmaceutical composition according to claim 4 suitable for the treatment and prevention of thromboembolic disorders, for the prevention of arteriosclerosis and metastasis and for treating ischaemia, asthma and allergies. 
     
     
       6. Pharmaceutical composition according to claim 4 suitable for the treatment and prevention of diseases in which thromboxane-mediated constriction or PGE 2  -mediated dilation of the capillaries are involved, in order to reduce the severity of transplant rejection, to reduce renal toxicity of substances such as cyclosporin, for treating kidney diseases and for treating states of shock. 
     
     
       7. Pharmaceutical composition according to claim 4, or 6, characterised in that it additionally contains as active substance a PDE inhibitor or a lysing agent.